Dengue vaccine research
Dengue is a mosquito-borne flavivirus disease that has spread to most tropical and many subtropical areas. The disease is caused by four closely related viruses, the Dengue viruses 1-4. There are no specific dengue therapeutics and prevention is currently limited to vector control measures. A dengue vaccine would therefore represent a major advance in the control of the disease.
Status of vaccine development
While no licensed dengue vaccine is available, several vaccine candidates are currently being evaluated in clinical studies.
The candidate currently at the most advanced clinical development stage, a live-attenuated tetravalent vaccine based on chimeric yellow fever-dengue virus (CYD-TDV), has progressed to phase III efficacy studies.
Results from a phase III multicentric efficacy study in Asia have been published in July 2014.
Results from a phase IIb efficacy study in Thailand have been published in September 2012.
Several other live-attenuated vaccines, as well as subunit, DNA and purified inactivated vaccine candidates, are at earlier stages of clinical development. Additional technological approaches, such as virus-vectored and VLP-based vaccines, are under evaluation in preclinical studies.
Challenges to vaccine development
Infection by one of the four dengue virus serotypes has been shown to confer lasting protection against homotypic re-infection, but only transient protection against a secondary heterotypic infection. Moreover, secondary heterotypic infection is associated with an increased risk of severe disease. This and other observations suggest an immunopathological component in dengue pathogenesis, which is referred to as immune enhancement of disease. Due to these dengue-specific complexities, vaccine development focuses on the generation of a tetravalent vaccine aimed at providing long-term protection against all virus serotypes. Additional challenges are posed by the lack of an adequate animal disease model and the resulting uncertainty around correlates of protection. In spite of these challenges, vaccine development has made remarkable progress in recent years, and the current dengue vaccine pipeline is advanced, diverse and overall promising.
The WHO Initiative for Vaccine Research (IVR), in collaboration with a wide range of partners, aims to facilitate the development and future introduction of safe, effective and affordable dengue vaccines. Activities focus on the following main objectives:
- Identify knowledge gaps and research needs related to the development, evaluation and implementation of dengue vaccines
- Build scientific consensus and develop guidance on the evaluation of dengue vaccines
- Review and evaluate the evidence base for policy recommendations related to the introduction and use of dengue vaccines
- Develop guidance on vaccine implementation, including introduction strategies
IVR is part of the Dengue Vaccine Initiative (DVI), a collaborative effort of partners to facilitate the introduction of future dengue vaccines.
Related WHO guidelines
- Guidelines for the clinical evaluation of dengue vaccines in endemic areas (2008)
- Guidelines for plaque reduction neutralization testing of human antibodies to dengue viruses (2007)
- Dengue: Guidelines for diagnosis, treatment, prevention and control (2009)
Related WHO meeting reports
Next generation dengue vaccines (2011)
- Dengue modeling (2011)
- Cell mediated immunity in dengue vaccine development (2008)
- Immune correlates of protection induced by dengue vaccines (2007)
More information on vaccine candidates
Q&A: Phase IIb study of CYD-TDV (September 2012)
- Special Issue: The development of dengue vaccines (Vaccine, Volume 29, Issue 42, Pages 7219-7284, 23 September 2011)
- WHO Technical Advisory Group on Dengue Vaccines in Late Stage Development
- WHO Fact sheet: Dengue and severe dengue
- WHO Global strategy for dengue prevention and control, 2012-2020
- Other WHO activities on dengue
- Dengue Vaccine Initiative (DVI)
- U.S. Centers for Disease Control and Prevention: Dengue Branch